19-48491478-G-A

Position:

• chr19-48491478-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001388485.1(LMTK3):​c.4154C>T​(p.Thr1385Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000789 in 1,268,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: LMTK3 NM_001388485.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85

Genes affected

LMTK3 (HGNC:19295): (lemur tyrosine kinase 3) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be located in Golgi membrane; axon; and dendrite. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33434576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMTK3	NM_001388485.1	c.4154C>T	p.Thr1385Met	missense_variant	13/15	ENST00000600059.6
LMTK3	NM_001080434.2	c.4154C>T	p.Thr1385Met	missense_variant	14/16
LMTK3	XM_011526411.3	c.4232C>T	p.Thr1411Met	missense_variant	14/16
LMTK3	XM_011526412.3	c.4199C>T	p.Thr1400Met	missense_variant	14/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMTK3	ENST00000600059.6	c.4154C>T	p.Thr1385Met	missense_variant	13/15	2	NM_001388485.1	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.89e-7 AC: 1 AN: 1268106 Hom.: 0 Cov.: 33 AF XY: 0.00000161 AC XY: 1 AN XY: 619212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000171

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0092	T;.;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.60	T;T;T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	0.95	N
PrimateAI	Pathogenic	0.86	D
Sift4G	Uncertain	0.032	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.41
MutPred		0.26		Loss of glycosylation at T1385 (P = 4e-04);.;.;
MVP		0.62
ClinPred		0.87	D
GERP RS		3.5
Varity_R		0.071

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1226439431; hg19: chr19-48994735;